Measurement of glucose in solution in body fluids is usually carried out by measuring the consequence of oxidation of the glucose in the body fluid. This oxidation may be catalyzed by an enzyme, e.g., glucose oxidase.
The glucose oxidase reaction is as follows: ##EQU1##
Several configurations of electrodes using this reaction which might be applied to body fluids have been suggested to the art.
According to a suggestion made by Clark et al., a polarographic oxygen electrode is placed behind a chamber filled with a solution of glucose oxidase. The outer wall of the chamber is permeable to glucose and oxygen, and the wall of the chamber facing the oxygen electrode is permeable only to oxygen. When a glucose solution is applied to the outer membrane, the glucose oxidase reaction consumes oxygen, diminishing the reading of the oxygen electrode as some function of the glucose concentration. For details of this suggestion, see L. C. Clark, Jr. and E. W. Clark. "Differential Anodic Enzyme Polarography for the Measurement of Glucose", Adv. Exp. Med. Biol. 37A, 127-133 (1973).
According to a suggestion made by Updike and Hicks, two polarographic oxygen electrodes are placed behind two cylinders of gel. One cylinder of gel contains entrapped vacuoles of glucose oxidase solution and the other acts as a control. The amount of glucose in a solution is determined as a function of the difference in the reading of the two electrodes, only one of which is affected by the presence of glucose in a similar manner to the Clark electrode. See Updike, S. J. and Hicks, G. P. "The enzyme electrode, a miniature chemical transducer using immobilized enzyme activity". Nature 214, 986 (1967) and also Wingard, Jr., L. B., Schiller, J. G., Wolfson, Jr., S. K., Liu, C. C., Drash, A. L. and Yao, S. J. "Immobilized Enzyme Electrodes for the Potentiometric Measurement of Glucose Concentration". J. Biomed. Mat. Res. 13, 921-935, (1979).
Another suggestion is for a differential electrode using two galvanic oxygen cells, one of which is a reference and the other covered by a plastic membrane containing covalently bonded glucose oxidase in a closed loop "artificial beta cell" as well as for other measurements. See Layne, E. C., Schultz, R. D., Thomas, Jr., L. J., Slama, G., Sayler, D. F. and Bessman, S. P. "Continuous Extracorporeal Monitoring of Animal Blood Using the Glucose Electrode". Diabetes 25, 81-89 (1976).
Still another suggestion is for an electrode which uses glucose oxidase to form peroxide which is read directly using a polarographic cell. See Chua, K. S. and Tan, F., "Plasma Glucose Measurement with the Yellow Springs Glucose Analyzer". Clin. Chem. 24, 150-152 (1978).
One suggested measurement for glucose relies on heat generated by the above reaction. Suggested has been an electrode which measures temperature of the glucose oxidase using a very sensitive thermistor covered with a layer of glucose oxidase. See Danielsson, B., Mattiason, B., Karlsson, R. and Winquist, F. "Biotechnology and Bioengineering," Vol. XXI, Pg. 1749-1766 (1979) John Wiley and Sons, Inc.
One way or another, all of the suggestions made heretofore, such as those alluded to above, assume that the actual level of dissolved oxygen in the body fluid is of no significant consequence to the glucose measurement since only the changes in one reactant or another, as indicated by oxygen utilization or formation of peroxide, by generation of heat, or of gluconic acid are indicative of glucose concentration.
However, availability of oxygen for reaction with glucose, i.e., actual oxygen concentration in the body fluid is a limiting factor for the glucose oxidation reaction. Yet, as has been pointed out above, the art has not heretofore accounted for limitations imposed by availability of oxygen on the electrode systems which depend on glucose oxidation for measuring glucose content in body fluid.